Choline – An Essential Nutrient

Choline is an essential nutrient that a lot of us don’t get enough of. In fact, the majority of the US population doesn’t get enough choline on a daily basis. Insufficient choline can impact mental sharpness, heart health, fatty liver disease, and more. [ref]

This article digs into the research on the various different forms of choline and how genetic variants impact our need for choline. Genetics plays a big role in how well your body creates and uses choline.

Why do we need choline?

Choline is involved in several critical roles in the body including:

  • supporting methylation reactions through donating a methyl group
  • formation of acetylcholine, a neurotransmitter and cell-signaling molecule
  • formation of phosphatidylcholine which makes up cell membranes[ref]
  • muscle function [ref]
  • deficiency in choline contributes to non-alcoholic fatty liver disease[ref]

Recent studies of choline show:

  • Academic achievement in 15-year olds is significantly associated with plasma choline levels[ref] Wow – I have a hard time wrapping my head around the idea that a nutrient can be that important for academic achievement.
  • Choline plus B-vitamins may increase neuroplasticity and speed recovery after a stroke [ref]
  • Choline deficiency is correlated to lower bone mineral density [ref]

Making choline in the body vs. choline from food:

Generally, people can make some choline in their liver. This is not enough choline to meet all the needs of the body, though, so it is essential to also get choline via the diet.  Additionally, some people have genetic variants that reduce their ability to make choline, thus increasing their need for choline from food.

The FDA recommends an adequate intake for adults of 425-550 mg/day for choline.   [ref]

Acetylcholine – an important neurotransmitter:

Choline is the precursor to acetylcholine, which is an important neurotransmitter. Acetylcholine is the signaling molecule for neurons that control muscles, heart rhythm, and other function.

Choline in the methylation cycle:

Your body’s need for choline from the diet will depend in part on how much folate you eat and how well your methylation cycle works.  Choline acts as a methyl donor in the methylation cycle, and with low folate or decreased enzyme efficiency in the folate pathways, your choline requirement may increase.

Specifically, choline in the form of betaine (also known as trimethylglycine) acts as a methyl donor within the methylation cycle.[ref]

When choline levels are low, homocysteine levels can increase, which is associated with an increased risk of cardiovascular disease.  Increasing levels of betaine in the diet are linked with lower homocysteine levels. [ref]

A study published in the American Journal of Clinical Nutrition found that with just two weeks of supplemental choline (2.6 g/day as phosphatidylcholine), homocysteine levels dropped by 18% compared to placebo.[ref]

Choline for the brain:

Choline is a precursor for acetylcholine, a neurotransmitter involved in learning and memory. Acetylcholine is essential for healthy cognitive function. Simply put, we need choline to think and function well. [ref]

In a mouse model of Alzheimer’s disease, giving the mice choline for most of their life reduced the Alzheimer’s pathology. [ref] Yes – this is just a mouse study. But the cholinergic system is important in Alzheimer’s disease, and commonly used medications for Alzheimer’s include acetylcholinesterase inhibitors.

Fatty liver disease and choline deficiency:

A study of 57 normal adults investigated the effects of limiting either choline from the diet or folate from the diet for a period of 6-weeks.  The study found that 77% of postmenopausal women and 80% of men developed fatty liver disease in the six weeks of choline deprivations (<50mg/day). No significant changes were found from limiting folate in the diet.  [ref]

Choline requirements in pregnancy:

Choline is an essential component of cell membranes, so a developing fetus needs a lot of choline. Women who are pregnant or nursing thus have a greater need for choline. When pregnant, a woman will produce more choline, which is then transported to the developing baby. So despite the increased production of choline, pregnant women end up low in choline.  Breast milk is also high in choline, so nursing the baby also depletes the mother of choline. [ref]


Genetic variant that impact choline

PEMT gene:

The PEMT gene codes for the enzyme phosphatidylethanolamine N-methyltransferase. The PEMT pathway is responsible for the body’s production of phosphatidylcholine, which is part of the phospholipid bilayer making up the membranes surrounding our cells. The PEMT enzyme is key in the body’s ability to create choline. Genetic variants that decrease the function of the enzyme cause a greater reliance on choline from dietary sources.

Check your genetic data for rs7946 V175M (23andMe v4, v5; AncestryDNA)

  • C/C: normal PEMT activity (most common genotype worldwide)
  • C/T: somewhat decreased PEMT enzyme activity
  • T/T: decreased PEMT enzyme activity [ref] increased risk of non-alcoholic fatty liver disease in lean people[ref][ref] ( most common genotype for Caucasian populations)

Check your genetic data for rs12325817 (AncestryDNA)

  • C/C: typical
  • C/G: increased risk of organ dysfunction with low choline diet
  • G/G: significantly increased risk of organ dysfunction with low choline diet[ref]

CHKA gene:

The CHKA gene codes for the choline kinase alpha enzyme, which is involved in the pathway of reactions that converts choline into phosphatidylcholine (needed for cell membranes). Choline kinase specifically is the catalyst in the reaction that converts choline into O-phosphocholine.   The variant below decreases the turnover of dietary methionine into choline. Carriers of the variant are more likely to need dietary choline since they don’t convert dietary protein (methionine) into choline very well.

Check your genetic data for rs10791957 (23andMe v4, v5; AncestryDNA)

  • A/A: reduced turnover of methionine to phosphatidylcholine [ref] [ref]
  • A/C: reduced turnover of methionine to phosphatidylcholine
  • C/C: typical

 

BHMT  Gene:

The BHMT gene codes for the Betaine-homocysteine S-methyltransferase enzyme.

Check your genetic data for rs3733890 (23andMe v4, v5; AncestryDNA):

  •  A/A: lower conversion of choline to betaine and more conversion of choline to CDP-PC [ref]
  • A/G: lower conversion of choline to betaine and more conversion of choline to CDP-PC
  • G/G: typical

FMO3 – Flavin-containing monooxygenase

Check your genetic data for rs2266782 (23andMe v4, v5):

  • A/A: a greater turnover of betaine to methionine and a greater turnover of choline-derived methionine to PEMT-PC[ref]
  • A/G:  a greater turnover of betaine to methionine and a greater turnover of choline-derived methionine to PEMT-PC
  • G/G: typical

 

MTHFD1 gene:

The MTHFD1 gene codes for the enzyme called methylenetetrahydrofolate dehydrogenase, cyclohydrolase and formyltetrahydrofolate synthetase 1.This is actually an enzyme in the folate pathway, but it affects your need for adequate choline in the diet.

Check your genetic data for rs2236225 (G1958A): (23andMe v4, v5; AncestryDNA)

  • A/A: decreased MTHFD1 enzyme stability[ref] more of a reliance on choline as a methyl donor [ref] [ref]
  • A/G: decreased MTHFD1 enzyme stability[ref] more of a reliance on choline as a methyl donor
  • G/G: typical

Carriers of the A allele are more likely to have choline deficiency on a low choline diet (modified by folate intake) [ref] [ref]  In one study with premenopausal women, those with an A-allele were 15 times more likely to show choline deficiency symptoms on a diet low in choline.


Lifehacks

Food sources:

Excellent (egg-cellent :-) sources of choline in foods include:  eggs, liver, shitake mushrooms, milk, and various meats.[ref]

Food sources of choline – National Institute of Health, Health Professionals Fact Sheet
Food Mg per
serving
Percent
DV
Beef liver, pan fried, 3 ounces 356 65
Egg, hard boiled, 1 large egg 147 27
Beef top round, separable lean only, braised, 3 ounces 117 21
Soybeans, roasted, ½ cup 107 19
Chicken breast, roasted, 3 ounces 72 13
Beef, ground, 93% lean meat, broiled, 3 ounces 72 13
Fish, cod, Atlantic, cooked, dry heat, 3 ounces 71 13
Mushrooms, shiitake, cooked, ½ cup pieces 58 11
Potatoes, red, baked, flesh and skin, 1 large potato 57 10
Wheat germ, toasted, 1 ounce 51 9
Beans, kidney, canned, ½ cup 45 8
Quinoa, cooked, 1 cup 43 8
Milk, 1% fat, 1 cup 43 8
Yogurt, vanilla, nonfat, 1 cup 38 7

Meat and eggs are the most abundant sources of choline — but even so, a serving of chicken breast gives you 13% of the recommended daily value.

If you want to know how much choline you normally get in your diet, you should track what you eat for a week or so.  The free online app, cronometer.com, includes the choline content of foods. Choline content isn’t enabled by default, so you will need to go into the settings and turn on ‘choline’.

Supplements:

There are several options for choline if you are looking to optimize your cognition and mental clarity. It is one of the basic brain-building blocks and the basis for acetylcholine. Raw choline donor help with brain energy.

Choline supplement options include CDP-choline, phosphatidylcholine, alpha-GPC, and choline citrate.  Examine.com is a good source of information on the different types of choline.

  • Choline bitartrate – simple and cheap source of choline, but not all that effective at crossing the blood brain barrier in people.
  • Alpha GCP – can cross the blood brain barrier.  Alleviates impaired memory.
  •  CDP Choline – both choline plus uridine precursor.

 

More to read:

Linus Pauling Institute (University of Oregon) – Choline

Originally published 5/2017. Updated 1/2020.



Author Information:   Debbie Moon
Debbie Moon is the founder of Genetic Lifehacks. She holds a Master of Science in Biological Sciences from Clemson University. Debbie is a science communicator who is passionate about explaining evidence-based health information. Her goal with Genetic Lifehacks is to bridge the gap between scientific research and the lay person's ability to utilize that information. To contact Debbie, visit the contact page.